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An attenuated strain of Bacillus anthracis (CDC 684) has a large chromosomal inversion and altered growth kinetics

Okinaka, Richard T., Price, Erin P., Wolken, Spenser R., Gruendike, Jeffrey M., Chung, Wai Kwan, Pearson, Talima, Xie, Gary, Munk, Chris, Hill, Karen K., Challacombe, Jean, Ivins, Bruce E., Schupp, James M., Beckstrom-Sternberg, Stephen M., Friedlander, Arthur and Keim, Paul (2011). An attenuated strain of Bacillus anthracis (CDC 684) has a large chromosomal inversion and altered growth kinetics. BMC Genomics,12(1):477-489.

Document type: Journal Article
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Title An attenuated strain of Bacillus anthracis (CDC 684) has a large chromosomal inversion and altered growth kinetics
Author Okinaka, Richard T.
Price, Erin P.
Wolken, Spenser R.
Gruendike, Jeffrey M.
Chung, Wai Kwan
Pearson, Talima
Xie, Gary
Munk, Chris
Hill, Karen K.
Challacombe, Jean
Ivins, Bruce E.
Schupp, James M.
Beckstrom-Sternberg, Stephen M.
Friedlander, Arthur
Keim, Paul
Journal Name BMC Genomics
Publication Date 2011
Volume Number 12
Issue Number 1
ISSN 14712164   (check CDU catalogue open catalogue search in new window)
Start Page 477
End Page 489
Total Pages 13
Place of Publication London, U.K
Publisher BioMed Central Ltd.
Abstract Background
An isolate originally labeled Bacillus megaterium CDC 684 was found to contain both pXO1 and pXO2, was non-hemolytic, sensitive to gamma-phage, and produced both the protective antigen and the poly-D-glutamic acid capsule. These phenotypes prompted Ezzell et al., (J. Clin. Microbiol. 28:223) to reclassify this isolate to Bacillus anthracis in 1990.

Results

We demonstrate that despite these B. anthracis features, the isolate is severely attenuated in a guinea pig model. This prompted whole genome sequencing and closure. The comparative analysis of CDC 684 to other sequenced B. anthracis isolates and further analysis reveals: a) CDC 684 is a close relative of a virulent strain, Vollum A0488; b) CDC 684 defines a new B. anthracis lineage (at least 51 SNPs) that includes 15 other isolates; c) the genome of CDC 684 contains a large chromosomal inversion that spans 3.3 Mbp; d) this inversion has caused a displacement of the usual spatial orientation of the origin of replication (ori) to the termination of replication (ter) from 180° in wild-type B. anthracis to 120° in CDC 684 and e) this isolate also has altered growth kinetics in liquid media.

Conclusions

We propose two alternative hypotheses explaining the attenuated phenotype of this isolate. Hypothesis 1 suggests that the skewed ori/ter relationship in CDC 684 has altered its DNA replication and/or transcriptome processes resulting in altered growth kinetics and virulence capacity. Hypothesis 2 suggests that one or more of the single nucleotide polymorphisms in CDC 684 has altered the expression of a regulatory element or other genes necessary for virulence.

Keywords Bacillus megaterium CDC 684
pXO1
pXO2
Bacillus anthracis
DOI http://dx.doi.org/10.1186/1471-2164-12-477   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)


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Created: Tue, 27 Nov 2012, 16:01:10 CST by Teresa Haendel